CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beichen West Road, Beijing 100101, China.
Nat Commun. 2011 Dec 6;2:577. doi: 10.1038/ncomms1571.
Multiple surface envelope proteins are involved in the human herpes simplex virus type 1 entry and fusion. Among them, glycoprotein D (gD) has an important role by binding to the host receptors such as herpes virus entry mediator and nectin-1. Although the complex structure of gD with herpes virus entry mediator has been established, the binding mode of gD with the nectin-1 is elusive. Nectin-1 is a member of the immunoglobulin (Ig)-like (three Ig-like domains) cell adhesion molecules and is believed to form a homodimer to exert its functions. Here we report the complex structure of gD and nectin-1 (three Ig domains), revealing that gD binds the first Ig domain of nectin-1 in a similar mode to the nectin-1 homodimer interaction. The key amino acids responsible for nectin-1 dimerization are also used for gD/nectin-1 binding. This result indicates that binding of gD to nectin-1 would preclude the nectin-1 dimerization, consequently abolishing its cell adhesion function.
多种表面包膜蛋白参与了人类单纯疱疹病毒 1 型的进入和融合。其中，糖蛋白 D（gD）通过与疱疹病毒进入介质和 nectin-1 等宿主受体结合，发挥着重要作用。尽管 gD 与疱疹病毒进入介质的复合物结构已经建立，但 gD 与 nectin-1 的结合模式仍难以捉摸。Nectin-1 是免疫球蛋白（Ig）样（三个 Ig 样结构域）细胞黏附分子家族的一员，被认为形成同源二聚体以发挥其功能。在这里，我们报告了 gD 和 nectin-1（三个 Ig 结构域）的复合物结构，揭示了 gD 以类似于 nectin-1 同源二聚体相互作用的方式结合 nectin-1 的第一个 Ig 结构域。负责 nectin-1 二聚化的关键氨基酸也用于 gD/nectin-1 结合。这一结果表明，gD 与 nectin-1 的结合会阻止 nectin-1 的二聚化，从而使其丧失细胞黏附功能。
